Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen in the U.S. with an estimated 20 million cases annually. Studies have been in progress to define the clinical spectrum of chlamydial infection, to develop rapid diagnostic assays, and to examine the pathogenesis of chlamydial infections in experimental animal models. In women, chlamydia cervical infection continues to be high (20-30%). Coinfection with gonorrhea and human papillomavirus frequently occur and are strongly associated with the appearance of cervical dysplasia and cervical carcinoma. In a study to determine the reliability of mucopurulent cervicitis (MPC) as a predictive sign for chlamydia infection we found that 51% of patients with MPC had gonococcal cervicitis and 44% had chlamydial cervicitis, while 28% had both. Contrary to previous studies, no significant association between chlamydia and polymorphonuclear leukocytes or with MPC could be established. The positive predictive value of MPC for chlamydial infection was only 44% due to the frequent occurrence of other infections such as gonorrhea and trichomonas. Studies have been initiated to examine the impact of contraceptives of the recurrence of chlamydial infections. In a population with a chlamydia infection rate of 26% at time of enrollment, only 9% demonstrated infection following active use of contraceptives. Diagnostic assays including in situ hybridization utilizing DNA and RNA probes for C. trachomatis as well as polymerase chain-reaction have been initiated, and a high sensitivity and specificity for detection of chlamydia in tissue samples have been documented. A series of investigations concerning biology and pathogenesis of the TWAR strain of chlamydia re currently in progress. We have demonstrated that optimal growth of TWAR is achieved in HeLa cells following 120 hour incubation, and that TWAR can be detected with monoclonal antibodies directed at the lipopolysaccharide antigen of chlamydia. Inoculation of cynomolgus monkeys with TWAR demonstrated establishment of mucosal infections of the eye, nasopharynx, and intestine, followed by a serologic immune response to the infecting agent. Further studies are planned to examine the clinical spectrum of chlamydia infections and the immunopathogenesis of this pathogen in non-human primate models.